This program involves the development of various forms of high performance liquid chromatography and the application of the methodologies to problems of biomedical and clinical significance. Our efforts include the study of ion pair partition liquid chromatography and its application to the analysis of sulfa drugs, folic acid and derivatives, and other ionizable substances. General reverse phase liquid chromatography has been employed in the analysis of indole substances and porphyrins. A method has been developed for the analysis of free (i.e. unbound) thyroid hormone fractions using equilibrium dialysis and gas chromatography with electron capture detection. Detection limits as low as 0.2 pg are achievable, and this means that the free thyroid hormones can be readily determined in one ml of serum. Research now involves the application of this method to pathological sera. BIBLIOGRAPHIC REFERENCES: S. S. Su, A. V. Hartkopf and B.L. Karger, J. Chromatog., 119, 523 (1976). "High Performance Ion-Pair Partition Chromatography of Sulfa Drugs. Study and Optimization of Chemical Parameters". A.P. Graffeo and B.L. Karger, Clin. Chem., 22, 184 (1976). "Analysis for Indole Compounds in Urine by High-Performance Liquid Chromatography with Fluorometric Detection".